Outpatient 5-fluorouracil, folinic acid and cisplatin in patients with advanced esophageal carcinoma.

In a multicenter phase II study, 30 patients with unresectable, locally advanced or metastatic squamous cell or adenocarcinoma of the esophagus were treated with folinic acid 200 mg/m2/d, 5-FU 300 mg/m2/d, and cisplatin 20 mg/m2/d intravenously for 5 days every 4 weeks. Two of 13 patients with squamous cell carcinoma (SCC) had a complete response (CR), but one died of pneumonia after 9 months while still in CR, and the other still in CR after more than 5 years. Six other patients (3 SCC, 2 of 16 with adenocarcinoma, 1 mixed histology) had a partial response with a median duration of 9 months (range 5 to 57 + months) for an overall response rate of 27%. A further 6 patients (20%) had stable disease. Grade 4 neutropenia occurred in 6 patients (20%), with 5 requiring antibiotics for associated fever. Other grade 4 toxicities were nausea and vomiting (1), anemia (1), and thrombocytopenia (1); there were three early deaths (emphysema, cardiac arrest, pulmonary embolism). This combination appears to be an active, convenient regimen for advanced esophageal cancer, resulting in prolonged remission and survival in some patients.

Quantitative Phenotyping of Childhood Leukemia Identifies Variable and Invariable Cell Surface Antigens.

Cells obtained from 75 cases of childhood leukemia were subjected to flow cytometry analysis to estimate the density of several cell surface antigens and derive a quantitative immunological phenotype. Sixty-five cases of acute lymphoblastic leukemia (ALL) including 10 T-ALL, 6 non-T ALL designated groups I and II (HLA-DRCALLA), 48 non-T ALL termed groups III and IV (HLA-DRCALLA) and one B-ALL were studied; 10 cases of acute myeloblastic leukemia (AML) were also analysed. The estimation of the relative fluorescence index (RFI) on leukemic blasts led to the derivation of mean values for each marker in the leukemia subgroups. We have quantitated the levels of the antigens generally used in the classification of these leukemias (CALLA, CD5, CD20, CD13, HLA-DR and CD19) and of other cell surface antigens associated with leukemic cells. For example, CALLA (CD10) level was high (mean RFI value of 26.4) on the leukemic cells of non-T ALL groups III and IV. The CD5 antigen was present on T-ALL, as expected, with an RFI value of 4.5; however, low levels were observed on the more immature non-T ALL of groups I and II (RFI = 2.3 on only 27% of blast cells). The quantitative analysis of the cell surface antigens associated with non-T ALL has revealed molecules such as CALLA, HLA-DR, CD9 and CD44 present at high and variable levels and others such as CD19, CD38, 44G4, 44D7, 44H9 and 44H6 generally of lower intensity, less variable from one patient to another, and with similar mean levels of expression in the different subgroups. These invariable antigens are not altered by the lineage or stage of differentiation of the leukemic cells. The variable antigens could be correlated with the functional and/or differentiation status of the cells and could also be modified by the alterations of regulatory processes associated with malignancy. The quantitation of multiple leukemia-associated antigens, whose structure and function are becoming rapidly established, should help in elucidating the function of these molecules in leukemogenesis and/or disease progression.

Separation of lymphoid and myeloid blasts in the mixed blast crisis of chronic myelogenous leukemia: no evidence for Ig gene rearrangement in CALLA-positive blasts.

Recent studies suggest that lymphoid blast crisis cells of chronic myelogenous leukemia (CML) expressing the common acute lymphoblastic leukemia antigen (CALLA) are B precursor cells, based on the demonstration of immunoglobulin (Ig) gene rearrangement similar to common acute lymphocytic leukemia. There is little evidence to suggest whether the cells with similar lymphoid characteristics in the mixed blast crisis of CML are also committed to B cell lineage. A patient in "mixed" blast crisis of CML was studied. On the basis of morphology, cytochemistry, and immunological studies, the blasts were classified as having either lymphoid or myeloid characteristics. A proportion of the leukemic blasts expressed CALLA, whereas others expressed My7 antigen. In order to characterize both populations of cell further, CALLA+ blasts and My7+ (myeloid) blasts were isolated by fluorescence-activated cell sorting. The My7+ cells were highly proliferative in cell culture blast colony assays, retained the Ph1 chromosome, and were indistinguishable from acute myelogenous leukemia blasts. The CALLA+ cells were also Ph1-chromosome positive, but in contrast, were poorly proliferative in vitro. Of particular note was their retention of germline configuration of Ig genes, thus distinguishing them from blasts in the lymphoid crisis of CML. We conclude that the lymphoid component in mixed blast crisis may represent a stage of differentiation prior to commitment to B lineage.

Lineage specific classification of leukaemia: results of the analysis of sixty cases of childhood leukaemia.

In addition to conventional morphological, histochemical and immunological marker studies, cells from 60 children with leukaemia were further analysed using the Southern blot hybridization technique to look at differences in the organization of immunoglobulin (Ig) genes. Of the 60 patients studied by conventional means, 47 were diagnosed as acute lymphocytic leukaemia (ALL) and 13 as non-lymphocytic leukaemia. Seven patients were initially classified as T ALL and 40 as non-T, non-B ALL. Further subclassification of the 40 patients with non-T, non-B ALL indicated three pre-B ALL and 29 patients diagnosed as common ALL, expressing Ia and CALLA antigens. All 29 patients with common ALL demonstrated C mu gene rearrangements with or without light chain (kappa and lambda) genes rearrangement. Based on the developmental hierarchy of Ig gene rearrangement, it was possible to further subclassify the patients with common ALL into different stages of B cell development. Eight (of the 40) patients with non-T, non-B ALL were identified as CALLA- but further analysis indicated T-lineage origin in two patients and three patients were reclassified as acute undifferentiated leukaemia (AUL). C mu gene rearrangements were detected in two patients with T ALL, two patients with AUL and one patient with acute myelogenous leukaemia (AML). In contrast to the patients with common ALL, Ig gene rearrangement observed in these non-B-lineage cells was restricted to a single C mu gene while retaining germ-line configuration of the other allele of the C mu gene and both light chain genes.